Disease relevance of RGS3

• U373MG glioma cell clones overexpressing RGS3 or RGS4 showed an increase of both adhesion and migration [1].
• RGS3 and RGS4 gene expression was markedly enhanced in two model systems of cardiac hypertrophy: growth factor-stimulated cultured neonatal rat cardiomyocytes and pulmonary artery-banded (PAB) mice [2].
• This article provides detailed information on the use and power of retrovirus-mediated overexpression of RGS proteins in dorsal root ganglion neurons to isolate and identify the mechanisms underlying the initiation of RGS3-dependent inhibitory activity [3].
• In contrast, the distribution of PDZ-RGS3 does not change during heat stress [4].

High impact information on RGS3

• In dorsal root ganglion neurons overexpressing RGS3, we find that G protein signaling is rapidly terminated (or "desensitized") by calcium influx through voltage-gated channels [5].
• A naturally occurring variant of RGS3 that lacks the EF hand neither binds calcium nor produces rapid desensitization, giving rise instead to a slower calcium-dependent desensitization that is attenuated by a calmodulin antagonist [5].
• RGS3 mediates a calcium-dependent termination of G protein signaling in sensory neurons [5].
• In complex neural circuits subjected to abundant synaptic inhibition by G proteins (as occurs in dorsal spinal cord), rapid termination of inhibition by electrical activity by EF hand-containing RGS3 may ensure the faithful transmission of information from the most active sensory inputs [5].
• These data indicate that RGS3 inhibits G protein-coupled receptor signaling by a complex mechanism involving its translocation to the membrane in addition to its established function as a GTPase-activating protein [6].

Biological context of RGS3

• Regulators of G-protein signaling 3 and 4 (RGS3, RGS4) are associated with glioma cell motility [1].
• Employing yeast two-hybrid screening of a cDNA library, we identified an interaction between RGS3 and the phosphoserine-binding protein 14-3-3 [7].
• The coding region of the human RGS3 gene spans 14.7 kb and contains six exons, and the 5'-untranslated region spans 3.2 kb and contains two exons [8].
• By radiation hybrid mapping, the RGS3 gene was assigned to human chromosome 9q31-q33 [8].
• The existence of mRNAs of different size for some of the RGS proteins, e.g. RGS3, suggests that these proteins may exist in isoforms due to alternative splicing [9].

Anatomical context of RGS3

• Co-expression of RGS3 with Gbeta(1)gamma(2) inhibits Gbeta(1)gamma(2)-induced inositol phosphate production and Akt activation in COS-7 cells and mitogen-activated protein kinase activation in HEK 293 cells [10].
• A greater percentage of RGS3CT localized at the cell membrane than the full-length version, potentially explaining why RGS3CT blocked signaling better than did full-length RGS3 [11].
• An 80-kDa protein was identified as RGS3 by immunoprecipitation and immunoblotting with anti-RGS3 antibodies in a human mesangial cell line (HMC) stably transfected with RGS3 cDNA [6].
• Ribonuclease protection assays and Northern blot analysis showed two specific mRNAs for RGS3 (RGS3L, RGS3S) in human myocardium, suggesting an additional, N-terminally truncated form of approximately 168 aa [9].
• Using transiently transfected lymphoid cells as a model system, we show that expression of RGS1, RGS3, and RGS4 inhibits chemoattractant-induced migration [12].

Associations of RGS3 with chemical compounds

• Regulator of G-protein signaling 3 (RGS3) inhibits Gbeta1gamma 2-induced inositol phosphate production, mitogen-activated protein kinase activation, and Akt activation [10].
• The effect of endothelin-1 was also mimicked by calcium ionophore A23187, suggesting the importance of Ca2+ in the mechanism of redistribution of RGS3 [6].
• Palmitic acid incorporation into RGS3 was dependent on agonist occupancy of GnRHR, whereas palmitoylation of RGS10 was constitutive [13].
• C2PA is a novel protein that contains a C2 membrane binding domain, a PDZ protein/protein interaction domain, and an ATP/GTP binding domain [14].

Physical interactions of RGS3

• Here we show that RGS3 binds Gbeta(1)gamma(2) subunits and limits their ability to trigger the production of inositol phosphates and the activation of Akt and mitogen-activated protein kinase [10].

Regulatory relationships of RGS3

• These results suggest that the RGS3 gene may be involved in regulating G-protein signaling in olfactory receptor neurons [15].

Other interactions of RGS3

• RGS3 and RGS3CT had G(qalpha) GAP activity similar to that of RGS4 [11].
• Regulator of G-protein signaling 3 (RGS3) enhances the intrinsic rate at which Galpha(i) and Galpha(q) hydrolyze GTP to GDP, thereby limiting the duration in which GTP-Galpha(i) and GTP-Galpha(q) can activate effectors [10].
• Thus, RGS3 may limit Gbetagamma signaling not only by virtue of its GTPase-activating protein activity for Galpha subunits, but also by directly interfering with the activation of effectors [10].
• Consistent with the in vivo results, RGS3 inhibits Gbetagamma-mediated activation of phospholipase Cbeta in vitro [10].
• Thus, RGS3 can impair Gi- (but not Gz-) and Gq-mediated signaling in hematopoietic and other cell types by acting as a GAP for G(ialpha) and G(qalpha) subfamily members and as a potent G(qalpha) subfamily effector antagonist [11].

Analytical, diagnostic and therapeutic context of RGS3

• Using long-distance PCR, we amplified and characterized the entire coding and 5'-untranslated region of the human RGS3 gene [8].
• RT-PCR analysis demonstrated that this Medaka RGS3-like protein (MeRGS3L) is mainly expressed in skin and heart [16].
• Confocal microscopy was used to examine the intracellular locations of four RGS3-enhanced green fluorescent protein fusion proteins [17].

References